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EC number: 212-977-2 | CAS number: 897-06-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 176 µg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 4.41 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The leading health effect after repeated exposure of androstendion is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to inhalation is possible. The default assumption for differences in bioavailability between the two exposure routes (50 % of the substance will be absorbed after oral compared to inhalation exposure) is employed in this extrapolation. Further uncertainties related to toxicokinetics were taken into account by the factor 2.5 for remaining interspecies uncertainties.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already covered with correction of dose-descriptor.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 5
- Justification:
- For intraspecies variability, the default assessment factor for workers is 5.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 50 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- For androstendion it is not indicated that dermal absorption is higher than oral absorption, since at least acute toxicity studies reveal no findings at all after dermal exposure compared to unspecific and slight findings after oral exposure. Moreover, the leading health effect after repeated exposure is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to dermal route is justified.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- For allometric scaling rat to human the standard factor is 4
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 5
- Justification:
- For intraspecies variability, the default assessment factor for workers is 5.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Preliminary remarks
Androstadiendion (CAS No. 897-06-3) is an intermediate in the synthesis of different steroid hormones.
Since no repeated dose toxicity data are available for this substance, subchronic toxicity data of androstendion (CAS No.63-05 -8) were used for the DNEL derivation of androstadiendion. A search for structure-analogue substances using the QSAR Toolbox 3.3.5 recommended androstendion as one out of 11 category substances for a read-across approach (for details see QSAR OECD Toolbox Report on Androstadiendion attached in chapter 7, Endpoint Summary: Toxicological information).
In androstendion (androst-4-ene-3,17-dione) the double bound in position 1 of the target molecule androstadiendion (androsta-1,4-diene-3,17-dione) is replaced by a single bound. No other changes in the molecule occurred. No relevant toxicological effects are expected by the change of an alkene group versus an alkane group. Therefore, an identical toxicity profile of androstadiendion and androstendion is to be expected and a read-across with androstendion seems justified to fill the data gaps of androstadiendion.
Androstendion is an endogenous intermediate in steroid hormone synthesis and as such an endogenous precursor of testosterone and estrone, which can be metabolized to estradiol. Consequently, repeated exposure to the substance interferes with the body's hormonal balance (for a discussion on health effects see FDA white paper, Health Effects of Androstendione, 2004).
Selection of the relevant starting point for the derivation of systemic long-term DNELs (inhalation and dermal route) for workers
There are no repeated dose toxicity studies available with androstadiendion or androstendion for the dermal or inhalation route.
Two available subchronic (90-day) toxicity studies in rats and mice with oral administration of androstendion revealed evidence that the effect on fertility is the leading health effect of androstendion (NTP, 2010; Blystone et al., 2011). Whereas the rat study revealed a NOAEL of 5 mg/kg (based on sperm investigations: decreased number of sperm), mice were shown to be less susceptiple to reproductive toxicity of androstendione (based on sperm investigations: decreased sperm motility at 50 mg/kg). Therefore, the NOAEL of the rat study was used as point of departure for the derivation of systemic long-term DNELs for workers.
In addition, two carcinogenicity studies with androstendion were available (NTP, 2010; Blystone et al., 2011). The one on rats showed equivocal evidence and the one on mice clear evidence for carcinogenic activity. However, it has to be taken into account that steroid hormones in general can promote the growth of specific hormone dependent tissues and tumors. Furthermore, the overall conclusion of the available genotoxicity studies support that androstendion does not act as genotoxic carcinogen (Ames test - negative (Reimann,1996); HPRT - negative ( Wollny, 2013); MNT in vivo, rat - negative, male mouse - negative, female mouse - equivocal (NTP, 2010)). Therefore, despite the evidence of carcinogenic activity a threshold effect is concluded for androstendion and this threshold has to be related to reproductive toxicity/fertility. Consequently, for workers DNELs for long-term exposure via inhalation and dermal route have to be derived.
Derivation of a systemic long-term DNEL for workers on hazard via the inhalation route
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 3, Guidance Document R.8, ECHA, 2012):
In case of workers 8h/day exposed:
corrected inhalatory NOAEC =oral NOAEL * sRVrat-1* ABSoral-rat/ABSinh-human* sRVhuman/wRV
= oral NOAEL * (0.38 m³/kg bw)-1* 0.5 * 0.67 = 4.41 mg/m³
sRVrat= default respiratory volume rat, 8 h exposure = 0.38 m³/kg bw
ABSoral-rat/ABSinh-human= the absorption of rats after oral exposure is assumed to be 50 % of the human absorption after inhalation = 0.5
sRVhuman= standard respiratory volume human, 8 h exposure = 6.7 m³/person
wRV = respiratory volume light activity for worker, 8 h exposure = 10 m³/person
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the corrected NOAEC and are summarized in the table below:
Assessment |
Assessment Factor
|
For interspecies differences rat vs. human (allometric scaling) |
Already covered with correction of dose-descriptor |
For remaining interspecies differences1 |
2.5 |
For intraspecies differences (workers)2 |
5 |
Differences in duration of exposure3 |
2 |
Dose-response relationship4 |
1 |
Quality of whole Database5 |
1 |
Overall Assessment Factor |
25 |
1 A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
2 For intraspecies variability, the default assessment factor for workers is 5.
3 The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
4 When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
5 The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the
standard information requirements, is 1.
Therefore, the overall AF (assessment factor) is 25. Corrected inhalatory NOAEC : 25 = 0.176 mg/m³ = 176 µg/m³
DNELsystemic, long-term for workers for hazards via inhalation route = 176 µg/m³
Derivation of a systemic long-term DNEL for workers on hazards via the dermal route
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 5, Guidance Document R.8, ECHA, 2012):
In case of workers 8h/day exposed:
corrected dermal NOAEL = oral NOAEL * ABSoral-rat/ABSdermal-human = oral NOAEL * 1 = 5 mg/kg
ABSoral-rat/ABSdermal-human= the absorption of rats after oral exposure is assumed to be identical to the absorption of humans after dermal exposure = 1
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the NOAEL and are summarized in the table below:
Assessment |
Assessment Factor
|
For interspecies differences rat vs. human (allometric scaling)1 |
4 |
For remaining interspecies differences2 |
2.5 |
For intraspecies differences (workers)3 |
5 |
Differences in duration of exposure4 |
2 |
Dose-response relationship5 |
1 |
Quality of whole Database6 |
1 |
Overall Assessment Factor |
100 |
1 For allometric scaling rat to human the standard factor is 4.
2 A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
3 For intraspecies variability, the default assessment factor for workers is 5.
4 The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
5 When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
6 The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore, the overall AF (assessment factor) is 100. Corrected dermal NOAEL : 100 = 0.05 mg/kg = 50 µg/kg
DNELsystemic, long-term for workers for hazards via dermal route = 50 µg/kg bw/day
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 43 µg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 2.17 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The leading health effect after repeated exposure of androstendion is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to inhalation is possible. The default assumption for differences in bioavailability between the two exposure routes (50 % of the substance will be absorbed after oral compared to inhalation exposure) is employed in this extrapolation. Further uncertainties related to toxicokinetics were taken into account by the factor 2.5 for remaining interspecies uncertainties.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already covered with correction of dose-descriptor.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 25 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- For androstendion it is not indicated that dermal absorption is higher than oral absorption, since at least acute toxicity studies reveal no findings at all after dermal exposure compared to unspecific and slight findings after oral exposure. Moreover, the leading health effect after repeated exposure is the effect on fertility, based on the substance's interference with the body's hormonal balance. For such a systemic effect extrapolation from oral to dermal route is justified.
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- For allometric scaling rat to human the standard factor is 4
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 25 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- For allometric scaling rat to human the standard factor is 4
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, and is applied here for uncertainties related to toxicokinetics.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10.
- AF for the quality of the whole database:
- 1
- Justification:
- The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Preliminary remarks
Androstadiendion(CAS No. 897-06-3) is an intermediate in the synthesis of different steroid hormones.
Since norepeated dose toxicity data are available for this substance, subchronic toxicitydataof androstendion (CAS No.63-05 -8) were used for the DNEL derivation of androstadiendion.A search for structure-analogue substances using the QSAR Toolbox 3.3.5 recommended androstendion as one out of 11 category substances for a read-across approach (for details see QSAR OECD Toolbox Report on Androstadiendion attached in chapter 7, Endpoint Summary: Toxicological information).
In androstendion (androst-4-ene-3,17-dione) the double bound in position 1 of the target molecule androstadiendion (androsta-1,4-diene-3,17-dione) is replaced by a single bound. No other changes in the molecule occurred. No relevant toxicological effects are expected by the change of an alkene group versus an alkane group.Therefore, an identical toxicity profile of androstadiendion and androstendion is to be expected and a read-across with androstendion seems justified to fill the data gaps of androstadiendion.
Androstendion is an endogenous intermediate in steroid hormone synthesis and as such an endogenous precursor of testosterone and estrone, which can be metabolized to estradiol. Consequently, repeated exposure to the substance interferes with the body's hormonal balance (for a discussion on health effects see FDA white paper, Health Effects of Androstendione, 2004).
Selection of the relevant starting point for the derivation of systemic long-term DNELs (inhalation and dermal route) for the general population
There are no repeated dose toxicity studies available with androstadiendion or androstendion for the dermal or inhalation route.
Two available subchronic (90-day) toxicity studies in rats and mice with oral administration of androstendion revealed evidence that the effect on fertility is the leading health effect of androstendion (NTP, 2010; Blystone et al., 2011). Whereas the rat study revealed a NOAEL of 5 mg/kg (based on sperm investigations: decreased number of sperm), mice were shown to be less susceptiple to reproductive toxicity of androstendione (based on sperm investigations: decreased sperm motility at 50 mg/kg). Therefore, the NOAEL of the rat study was used as point of departure for the derivation of systemic long-term DNELs for the general population.
In addition, two carcinogenicity studies with androstendion were available (NTP, 2010; Blystone et al., 2011). The one on rats showed equivocal evidence and the one on mice clear evidence for carcinogenic activity. However, it has to be taken into account that steroid hormones in general can promote the growth of specific hormone dependent tissues and tumors. Furthermore, the overall conclusion of the available genotoxicity studies support that androstendion does not act as genotoxic carcinogen (Ames test - negative (Reimann,1996); HPRT - negative ( Wollny, 2013); MNT in vivo, rat - negative, male mouse - negative, female mouse - equivocal (NTP, 2010)). Therefore, despite the evidence of carcinogenic activity a threshold effect is concluded for androstendion and this threshold has to be related to reproductive toxicity/fertility. Consequently, for the general population DNELs for long-term exposure via inhalation and dermal route have to be derived.
Derivation of a systemic long-term DNEL for the general population on hazard via the inhalation route
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 3, Guidance Document R.8, ECHA, 2012):
In case of the general population 24h/day exposed:
corrected inhalatory NOAEC =oral NOAEL * sRVrat-1* ABSoral-rat/ABSinh-human
=oral NOAEL * (1.15 m³/kg)-1* 0.5 = 2.17 mg/m³
sRVrat= default respiratory volume rat, 24 h exposure = 1.15 m³/kg
ABSoral-rat/ABSinh-human= the absorption of rats after oral exposure is assumed to be 50 % of the human absorption after inhalation = 0.5
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the corrected NOAEC and are summarized in the table below:
Assessment |
Assessment Factor
|
For interspecies differences rat vs. human (allometric scaling) |
Already covered with correction of dose-descriptor |
For remaining interspecies differences1 |
2.5 |
For intraspecies differences (general population)2 |
10 |
Differences in duration of exposure3 |
2 |
Dose-response relationship4 |
1 |
Quality of whole Database |
1 |
Overall Assessment Factor |
50 |
1 A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
2 For intraspecies variability, the default assessment factor for the general population is 10.
3 The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
4 When the starting point for the DNEL delineation is a NOAEC, the default assessment factor, as a standard procedure, is 1.
5 The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore, the overall AF (assessment factor) is 50. Corrected inhalatory NOAEC : 50 = 0.043 mg/m³ = 43.5 µg/m³
DNELsystemic, long-term for the general population for hazards via inhalation route = 43.5 µg/m³
Derivation of a systemic long-term DNEL for the general population on hazards via the dermal/oral route
NOAEL = 5 mg/kg for rats exposed orally to the substance for 14 weeks, 5 days/week
Modification of dose-descriptor to the correct starting point (according to Example B. 5, Guidance Document R.8, ECHA, 2012):
In case of the general population 24h/day exposed:
corrected dermal NOAEL = oral NOAEL * ABSoral-rat/ABSdermal-human= oral NOAEL * 1 = 5 mg/kg
ABSoral-rat/ABSdermal-human= the absorption of rats after oral exposure is assumed to be identical to the absorption of humans after dermal exposure = 1
According to Guidance Document R.8 (ECHA, 2012) a series of assessment factors (AF) were applied to the NOAEL and are summarized in the table below:
Assessment |
Assessment Factor
|
For interspecies differences rat vs. human (allometric scaling)1 |
4 |
For remaining interspecies differences2 |
2.5 |
For intraspecies differences (general population)3 |
10 |
Differences in duration of exposure4 |
2 |
Dose-response relationship5 |
1 |
Quality of whole Database6 |
1 |
Overall Assessment Factor |
200 |
1 For allometric scaling rat to human the standard factor is 4.
2 A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences.
3 For intraspecies variability, the default assessment factor for the general population is 10.
4 The assessment factor suggested by Guidance Document R.8 (ECHA, 2012) for exposure duration from subchronic to chronic should be 2.
5 When the starting point for the DNEL delineation is a NOAEL, the default assessment factor, as a standard procedure, is 1.
6 The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Therefore, the overall AF (assessment factor) is 200. Corrected dermal NOAEL or oral NOAEL : 200 = 0.025 mg/kg = 25 µg/kg
DNELsystemic, long-term for the general population for hazards via dermal or oral route = 25 µg/kg bw/day
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.